Effect of long-term iodide refeeding on the synthesis and secretion of T3, T4 and TSH in severe iodine deficient rats.

Abstract

Abstract. For 6 months, male Wistar rats received an iodine deficient diet (LID), with propylthiouracil (PTU) for the last 2 months. At the end of this treatment (day 0), a daily iodide intake of 20 μg (group 20) and 50 μg (group 50) was supplied. Synthesis and secretion of T3, T4 and TSH as well as thyroid and serum PBI were studied during 140 days of iodine repletion. For the first 4 days of iodide refeeding, thyroid PBI remained low (0.4 ± 0.2 μg 127I/gland) whilst T3 and T4 were undetectable during 2 days only. Thereafter, these parameters increased regularly, reaching control values on days 80, 16 and 90, respectively. During 2 weeks, the thyroid T3/T4 ratio was 6-fold higher and reached the control value on day 45. Plasma T3 and T4 levels were low, but measurable for the first 4 days (0.5 ± 0.1 and 9.9 ± 2.6 nm, respectively). T3 rapidly reached a normal level on day 8, inducing a high plasma T3/T4 ratio for 16 days. This ratio decreased abruptly when T4 secretion increased, attaining the control value on day 45. Therefore, the preferential T3 secretion occurring during the first 16 days is directly linked to the preferential T3 synthesis. Plasma TSH levels remained 10-fold higher than the control value for the first 8 days (490 ± 99 vs 39 ± 15 μU/ml), then decreased abruptly and reached normal level after 1 month. Pituitary TSH contents varied in an opposite manner to the plasma TSH concentrations. In conclusion, the effect of iodide on thyroid function occurs sequentially, i.e. thyroid hormone synthesis precedes neosecretion (latency phase). In both processes, T3 appears preferentially. This phenomenon is linked to the low thyroglobulin (Tg) iodination rate. In addition, the re-establishment of a normal thyroid hormone secretion prevailing over the iodinated Tg store constitution represents an adaptative mechanism; this leads rapidly to a maximum supply of active hormone (T3) with iodine economy. Moreover, it takes 2–3 months for the complete thyroid function restoration. At the pituitary level, the normal plasma T3 concentration found during the latency phase of iodide refeeding is not sufficient by itself to inhibit TSH secretion. This parameter starts to decrease only when T4 has reached a critical level to generate adequate T3 from T4 deiodination. Inhibition of TSH synthesis is a less sensitive process since it occurs for more elevated T4 concentrations. Finally, the similar pattern of thyroid function's recovery in the two groups indicates that the 20 μg dose is a sufficient supply and that thyroid autoregulation occurs, thus avoiding a thyroid hyperfunction.